Brain-Gut peptides

Gut hormone-like neurotransmitters have been detected in the brain and are believed to function in a manner that 

Hypothalamic Peptide Neurotransmitter No. AA s GI Counterpart Functions in CNS Inferred or Postulated Functions in Gut 

Cholecystokininoctapeptide 8 CCK-33 T cellin Suppression of appetite Gallbladder contraction  

Gastrin 17 Gastrin-17 G cellsin stomach, duodenum Appetite regulation Gastric acid secretion viahistaminerelease from APUD cells in gastric mucosa (enterochromaffin-like (ECL) cells) (Hj antagonist-sensitive) 

Substance 11 Neural crest-derived cells, sensory C fibers Nociception Vasoconstriction (local effect) Mediates immune response to inflammation ) 

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GPR39 Brain-gut peptides Neuromedin U receptors ligands... 

Cholecystokinin (CCK) is one of the brain-gut peptides. Its most abundant form in the brain is the C-terminal sulphated octapeptide fragment CCK8, which interacts with the same affinity with both CCK receptor subtypes, CCK-A and CCK-B. Extensive pharmacological studies have been carried out over the last few years suggesting that CCK may participate in the neuroendocrine responses to stress (Harro et al 1993 Dauge and Lena 1998). Interestingly, CCK8 and CRH are co-locahzed in neurons of the hypothalamic PVN (Mezey etal. 1985). 

Brain/gut peptides angiotensin Ty2 argvasopressiu V1 bombesin CCK peripheral substance P substance K NPY Neurotensin Somatostatin VIP... 

Eysselein V, Eberlein G, Ho FJ, et al An amino-terminal fragment of cholecystokinin-58 is present in the gut evidence for a similar processing site of procholecystokinin in canine gut and brain. Reg Peptides 22 205-215, 1988 Fabre L, Vettraine J, Birkhimmer L, et al Fluvoxamine in the treatment of depression a double-blind comparison with imipramine and placebo in outpatients with major depression. Paper presented at the 18th CINP Congress, Nice, France, 1992... 

Another endogenous peptide which has been implicated in pain transmission and the central integration of pain responses is neurotensin (NeT) (Dobner, 2006 Gui et al., 2004 Pettibone et al., 2002). NeT is a brain-gut tridecapeptide that fulfils a dual function as a neurotransmitter/neuromodulator in the nervous system, and as a paracrine and circulating hormone at the periphery. Three NeT receptors, NTRl,... 

Like all neuropeptides, NT is synthesized as part of a larger precursor that also contains neuromedin N (NN), a 6 amino acid neurotensin-like peptide (Table 1). Pro-NT/NN is processed in the regulated secretory pathway of neuroendocrine cells by prohormone convertases PCI, PC2 and PC5-A that belong to a larger family of proprotein convertases. Due to differential cleavage specificity and tissue distribution of the convertases, pro-NT/NN processing gives rise to approximately a 1 1 and a 5 1 ratio of NT over NN content in the brain and gut, respectively. The peptides are stored in secretory vesicles and released from neuroendocrine cells in a Ca2+-dependent manner. NT and NN actions are terminated by desensitization of the... 

This peptide itself has no selectivity for the two CCK receptors, CCK-A and B, which have so far been established to stimulate IP3/DAG while, like substance P, can close potassium channels to increase neuronal activity. The CCK-B receptor is thought to predominate in the CNS but species differences may make this interpretation difficult. It has a wide distribution in the CNS but is also found in the gut whereas the CCK-A receptor is more restricted but is found in the hypothalamus, hippocampus and in the brainstem. There are high levels of the natural peptide, CCK-8 in cortex, hippocampus, hypothalamus, ventral tegmentum, substantia nigra, brainstem and spinal cord. CCK is one of the most abundant peptides in the brain and CCK co-exists with dopamine, substance P, 5-HT and vasopressin. Interestingly, in the dopamine areas, CCK co-exists in the mesolimbic pathways but in the nigrostriatal projections, the peptide and... 

The control of gut function involves interplay between neurones and peptide hormones. Information from a variety of receptors along the digestive tract is processed by a network of nerves, the enteric nervous system, which also receives input from the brain. 

In the brain, processing of the precursor leads primarily to the formation of NT and neuromedin N these are released together from nerve endings. In the gut, processing leads mainly to the formation of NT and a larger peptide that contains the neuromedin N sequence at the carboxyl terminal. Both peptides are secreted into the circulation after ingestion of food. Most of the activity of NT is mediated by the last six amino acids, NT(8-13). 

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